Lithium Hexamethyldisilazide → HCID 58465935, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with (S)-7′-bromo-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (200 mg, 0.509 mmol), chloro(2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butylether adduct (18.53 mg, 0.025 mmol), 4,4-difluoropiperidine hydrochloride (160 mg, 1.017 mmol) and 1 ml of THF. The mixture was cooled to 0° C. and LHMDS (1M in THF; 2035 μL, 2.035 mmol) was added. The vial was sealed and stirred at room temperature for 2 hr. At this point more chloro(2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butylether adduct (18.53 mg, 0.025 mmol), (18.53 mg, 0.025 mmol) was added followed by LHMDS solution (1 ml) and stirring was continued for another hour. The mixture was quenched by addition of 2 ml of water and extracted with ethyl acetate. The combined organic layers were concentrated and purified by chromatography (5-50% DCM/MeOH/NH4OH (90:10:1) to afford (S)-7′-(4,4-difluoropiperidin-1-yl)-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (130 mg, 0.300 mmol, 59.0% yield) as yellowish foam.

Provenance & Evidence